Cancer is a group of diseases involving the development of abnormal cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissue. It is the second-leading cause of death in the United States. Common types of cancer include lung cancer, prostate cancer, breast cancer, colorectal cancer, and cervical cancer. Although treatment options for cancer patients have increased steadily over the past decades, including surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care, cancer remains a top health threat and is responsible for about 15% of all human deaths.
Lung cancer is the second most common cancer, accounting for about 13% of all new cancer cases and account for around 27% of mortality of all cancers. NSCLC is the most common type of lung cancer. About 85%-90% of lung cancers are non-small cell lung cancers, which are histologically divided into sub-types of squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.
Treatment options for NSCLC are limited and often come with undesirable side effects. NSCLC remains one of the most difficult cancers to treat effectively. EGFR mutations occur in about 30% to 40% of NSCLCs in Asian patients and in about 15% of NSCLCs in western patients. First generation EGFR-TKIs, such as gefitinib and erlotinib, represent the best therapeutic option in first, second and maintenance setting for EGFR mutant patients. Virtually all patients, however, develop acquired resistance and, despite an initial benefit, progress due to the development of resistance. Among the molecular mechanisms responsible for acquired resistance are up-regulation of the downstream signal by mesenchymal-epidermal transition (MET) amplification and the emergence of T790M EGFR gatekeeper mutation. EGFR T790M mutation is responsible for resistance in around 60% of cases.
There is an urgent and growing need for innovative cancer therapeutics and treatment methods that can overcome acquired resistance, in particular resistance due to EGFR T790M mutation, leading to improved clinical effectiveness with reduced side effects.